Reye syndrome characteristically develops in the wake of a viral illness. diagnosis and management had improved since 1963 but an understanding of the pathogenetic link between the antecedent infection and the generalized mitochodrial injury is obscure. We propose a series of studies designed to uncover metabolic clues to the fundamental pathogenesis. During the acute illness we propose to study the temporal profile of several ciraculating metaboliltes and hormones. Components of the catecholamine (norepinephrine, epinephrine and dopamine), kallekrein-kinin (bradykinin) and renin-angiotensin (renin) systems will be assayed every six hours together with circulating free fatty acides, Beta-hyrdroxybutyrate, acetoacetate, glucose, lactate and pyruvate. These circulating substances will be measured by specific radioenzymatic, radioimmunological, or microfluorometric techniques which presently are established in the investigators' laboratories. After complete recovery or following brain-death, studies will be conducted on biopsied skeletal muscle (1) to measure adenine nucleotide (ATP, ADP, and AMP), phosphocreatine, carnitine and carnitine esters; and (2) to evaluate the integrity of the metabolic pathways involved in long chain and medium/short chain fatty acid oxidation and AMP resyntesis by the purine nucleotide cycle. We are searching for a metabolic defect in fatty acid oxidation or in the purine nucleotide cycle which will compromise the cellular energy charge during a period of metabolic/infectious stress. It is expected that a defect either in the oxidation of medium/short chain fatty acids or in the recycling of AMP would compromise the cellular energy charge during metabolic/infectious stress. Glycogen depletion and impaired biosynthesis of macromolecules might be expected under such conditions, as observed in Reye syndrome. The exaggerated release of vasoactive peptides might initiate this sequence by promoting excessive lypolysis and attendant free fatty acidemia. high circulating concentrations of bradykinin, if found, also would suggest high tissue concentrations of this hormone which is known to have edematogenic properties. Specific therapy could be comptemplated if any of the aforementioned speculations are corroborated by the planned experiments.